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1.
Toxicol In Vitro ; 98: 105849, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772494

RESUMO

Concerns over Bisphenol A (BPA) and its substitute, Bisphenol S (BPS), have led to innovative exploration due to potential adverse health effects. BPS, replacing BPA in some regions to avoid toxic impacts, remains insufficiently studied. Besides this, the organ-on-a-chip technology emerges as a transformative solution in drug discovery and chemiclas toxicity testing, minimizing costs and aligning with ethical standards by reducing reliance on animal models, by integrating diverse tissues and dynamic cell environments enhances precision in predicting organ function. Here, we employ a 3-organ-on-a-chip microfluidic device with skin, intestine, and liver cultures to assess the effects of BPA and BPS via topical and oral administration. Our evaluation focused on gene markers associated with carcinogenicity, systemic toxicity, and endocrine disruption. BPA exhibited expected absorption profiles, causing liver injury and genetic modulation in related pathways. BPS, a safer alternative, induced adverse effects on gene expression, particularly in topical absorption, with distinct absorption patterns. Our findings underscore the urgency of addressing BPA and BPS toxicity concerns, highlighting the crucial role of organ-on-a-chip technology in understanding associated health risks. The study promotes the organ-on-a-chip methodology as a valuable tool for safe drug development and disease treatments, offering a novel liver toxicity screening alternative to traditional animal tests. This contributes to advancing comprehension of the biological effects of these compounds, fostering improved safety assessments in human health.


Assuntos
Compostos Benzidrílicos , Dispositivos Lab-On-A-Chip , Fígado , Fenóis , Pele , Sulfonas , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Sulfonas/toxicidade , Animais , Pele/efeitos dos fármacos , Pele/metabolismo , Humanos , Intestinos/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Testes de Toxicidade/métodos , Sistemas Microfisiológicos
2.
Lab Chip ; 23(24): 5092-5106, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-37921576

RESUMO

Animal testing for cosmetic ingredients and final products has been banned in Europe and is gaining legal force worldwide. However, the need for reliable testing methodologies remains for safety assessment of cosmetic ingredients. While new approach methodologies exist for many toxicological endpoints, some complex ones lack appropriate testing methods. Microphysiological systems (MPSs) have emerged as a promising tool to address this gap in pre-clinical testing, offering higher predictivity compared to animal models due to the phylogenetic distance between humans and animals. Moreover, they provide a more physiological approach than traditional in vitro testing by mimicking interconnections between different culture compartments as seen in complex organisms. This study presents a three-organ microfluidic MPS comprising skin, liver, and intestine equivalents. Combining this model with gene expression analysis, we evaluated toxicological endpoints of chemicals, demonstrating its potential for diverse applications. Our findings highlight the MPS model as a reliable and ethical method to be applied in an integrated approach for safety assessment in the cosmetic industry. It offers a promising strategy to evaluate toxicological endpoints for cosmetic ingredients and other chemicals, supporting the elimination of animal testing while ensuring consumer safety.


Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos , Humanos , Animais , Sistemas Microfisiológicos , Filogenia , Transcriptoma , Cosméticos/toxicidade , Perfilação da Expressão Gênica
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